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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1989-02-17 to 1989-03-10
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
name of substance: 2,4-Dichlorotoluene
content: 99,4 % (analytical result dated November 30, 1988)
appearance: clear aqueous liquid
storage: refrigerator

Method

Target gene:
In the Salmonella typhimurium strains (TA 1535, TA 100, TA 1537, TA 1538, TA 98) the amino acid histidine locus is the target gene.
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Rat liver S-9 mix from Arochlor 1254 induced rats.
Test concentrations with justification for top dose:
0, 2.34, 9.38, 20, 37.5, 100, 150, 500, 600, 2400, 12500 µg/plate
Vehicle / solvent:
The solvent for 2,4-dichlorotoluene was ethanol and for the positive controls DMSO.
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
Ethanol
Positive controls:
yes
Positive control substance:
other: sodium azide (10 µg/plate - TA 1535); nitrofurantoin (0,2 µg/plate - TA 100); 4-nitro-1,2-phenylene diamine (10 µg/plate - TA 1537 and 0,5 µg/plate - TA 98); 2-aminoanthracene (3 µg/plate - all strains)
Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 100, and TA 98 this increase should be about twice the amount of negative controls, whereas for TA 1537 at least a threefold increase should be reached. Otherwise, the result is evaluated as negative.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Doses up to and including 9.38 µg/plate did not cause any bacteriotoxic effects. The range could only be used to a limit extent up to 2500 µg/plate for assessment purposes.
Vehicle controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
No indications of mutagenic effects of 2,4-dichlorotoluene could be found at assessable doses up to 2500 µg/plate in any of the Salmonella typhimurium strains used.
Executive summary:

In a reverse gene mutation assay in bacteria Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to 2,4-dichlortoluene at concentrations of 0, 2.34, 9.38, 20, 37.5, 100, 150, 500, 600, 2400, 12500 µg/plate in the presence and absence of mammalian metabolic activation.

Doses higher than 9.3 µg/plate had a strain-specific bacteriotoxic effect, but could partly be used for assessment up to and including 2500 µg/plate.

No indications of mutagenic effects of 2,4-dichlorotoluene could be found at assessable doses up to 2500 µg/plate in any of the Salmonella typhimurium strains used.